Efficacy, long‐term safety, and impact on quality of life of elobixibat in more severe constipation: Post hoc analyses of two phase 3 trials in Japan

Abstract

Background In two phase 3 trials, elobixibat, a locally acting ileal bile acid transporter inhibitor, resolved constipation and was well tolerated in Japanese patients with chronic constipation. We analyzed the efficacy, safety, and impact on quality of life (QOL) of elobixibat in patients with symptomatically more severe constipation in the two phase 3 trials. Methods This post hoc analysis of elobixibat treatment outcomes included data from a 2‐week, randomized, placebo‐controlled, phase 3 trial (10 mg/d), and a 52‐week, open‐label trial (5‐15 mg/d) in subgroups with severe constipation defined as ≤2 spontaneous bowel movements (SBMs) and ≤3 Bristol Stool Form Scale score during the second week of the 2‐week run‐in period. We also analyzed the rates of abdominal pain, diarrhea, and QOL in subgroups according to sex, presence of constipation‐predominant irritable bowel syndrome (IBS‐C) and side effects. Key Results In patients with severe constipation, there was significant improvement in the 10 mg elobixibat group compared to the placebo group in change in SBMs from baseline at week 1 (primary endpoint) of the 2‐week trial. The differences between groups were reduced in patients with more severe constipation. Increasing the dose to 15 mg was effective for more severe constipation in improving the number of SBMs per week in the 52‐week trial. Overall, elobixibat was well tolerated and improved QOL scores, irrespective of gender, presence of IBS‐C or side effects. Conclusions & Inferences Elobixibat is effective for symptomatically severe constipation, is well tolerated and improves QOL, irrespective of potentially confounding patient characteristics.

The duration of acupuncture effects and its associated factors in chronic severe functional constipation: secondary analysis of a randomized controlled trial

“…This result was partly similar with a recent post hoc analysis of two drug trials performed in Japan. 26 The latter analysis found participants in more severe condition needed a high dose of elobixibat and the treatment duration increased.…”

Uncontrolled, Open-Label Pre-Dinner Administration of Elobixibat in Japanese Adults with Chronic Constipation: A Retrospective Chart Review

“…Its efficacy was also consistent with the previous findings, although the examined duration is shorter than that of the Japanese long-term treatment studies that lasted up to 52 weeks. 12 , 19 Elobixibat increased the frequency of completely SBM; in other words, patients with constipation may defecate without a feeling of residual stool. In addition, elobixibat affects the threshold for intracolonic pressure or chemical stimulation for colonic mucosa.…”

Pregnancy complicated by refractory severe hypercholanaemia from sodium taurocholate co‐transporting polypeptide deficiency

“…Elobixibat is a new drug that has been approved for treatment of chronic constipation in Japan since 2018 21–23 . It is a highly selective partial inhibitor of the intestinal transporter located within the ileal mucosa, hence effectively disrupting the enterohepatic circulation 24 .…”

“…It is a highly selective partial inhibitor of the intestinal transporter located within the ileal mucosa, hence effectively disrupting the enterohepatic circulation 24 . It has shown minimal absorption into the systemic circulation after oral administration, and safety for use in doses up to 20 mg a day 21 . This results in increased BA concentrations within the intestinal lumen that has both a secretory and prokinetic effect in the treatment of chronic idiopathic constipation 25 .…”